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Biomedical subjects

P H Slee

Publications and source records attributed to P H Slee.

At least 19 recordsLinked to original sources
PubMed2004

[Clinical reasoning and decision making in practice. A depressive foreign woman with symptoms of malaise].

A 27-year-old woman was admitted to the hospital with a depression, anaemia and fatigue. She had come from Angola to the Netherlands as a refugee 2 years before this evaluation. As an explanation for her symptoms tropical infectious diseases of parasitic origin were considered, but no clues were found in this direction. The test for trypanosomiasis was considered to be suggestive for an infection in the past (persistent titre 1:200). She was discharged but readmitted 6 months later because of a deterioration of her clinical condition. Magnetic resonance imaging showed bilateral signal abnormalities within the white matter of the brain. On examination no neurological signs or abnormalities were found. Again, no definite diagnosis could be made and the patient was discharged. Because of a further deterioration of her clinical condition she was readmitted a short time later for the third time. On the MRI the white matter lesions had increased. The serum protein electrophoresis was markedly abnormal with an elevated IgM Level. Finally, at a repeated lumbar puncture mobile trypanosomes were found. The diagnosis of 'West African sleeping sickness' was made and the patient was treated with eflornithine. She recovered completely during the next 18 months.

Adult↗
PubMed2004

[High dose chemotherapy and stem cell transplant in patients with operable breast cancer and a poor prognosis; not indicated for the time being].

Early breast cancer with multiple tumour-positive axillary lymph glands is still characterised by a considerable mortality despite improvements in surgery, radiotherapy, chemotherapy and endocrine treatment. High-dose chemotherapy and bone-marrow support instead of the usual chemotherapy seemed to be a very promising approach back in the 1980s. Several phase-II studies supported this view and therefore phase-III studies were carried out. In a Cochrane review published at the start of 2003, a meta-analysis of several phase-III studies revealed that the results after high-dose chemotherapy were not significantly better than those after the usual treatment. Two large multicentre studies, one performed in the Netherlands and one in the USA, have recently been published. Neither of the two studies revealed survival differences, although one study demonstrated a significant benefit in actuarial 5-year relapse-free survival. Therefore, the routine clinical application of high-dose chemotherapy cannot be advocated yet.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group.

PURPOSE: Time to progression (TTP), overall survival, and quality of life (QL) were compared in patients with hormone-resistant prostate cancer (HRPC) treated with prednisone (5 mg orally, four times a day) or flutamide (250 mg orally, three times a day). PATIENTS AND METHODS: Symptomatic patients were randomized to receive either prednisone (101 patients) or flutamide (100 patients). Subjective response was assessed based on performance status, the use of analgesics, and the need to apply alternative palliative treatment. Prostate-specific antigen (PSA)-based biochemical response (>or= 50% reduction of baseline PSA) was recorded. At baseline and at 6-week intervals during follow-up, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30. RESULTS: There was no difference between the groups in median TTP (prednisone, 3.4 months; flutamide, 2.3 months) or overall survival (prednisone, 10.6 months; flutamide, 11.2 months). In the prednisone group, 56% of the patients experienced a subjective response, compared with 45% in the flutamide group (P: = .18). The median response duration was 4.8 months for prednisone and 4.2 months for flutamide. A biochemical response was observed in 21% and 23% of the prednisone and flutamide groups, respectively. Gastrointestinal toxicity was the reason for trial discontinuation in seven patients receiving flutamide and two patients receiving prednisone. The QL assessment parameters favored the use of prednisone with statistically significant differences in pain, fatigue, role functioning, appetite loss, gastrointestinal distress, and overall QL. CONCLUSION: In symptomatic HRPC, treatment with prednisone or flutamide leads to similar rates of TTP and overall survival and no difference in subjective or biochemical response. The QL results favor the use of low-cost prednisone in patients with HRPC.

Aged↗
PubMed2001

Is platinum-based chemotherapy with paclitaxel effective in optimally debulked patients with advanced ovarian cancer?

OBJECTIVE: Suboptimally debulked patients with advanced ovarian cancer who are treated with a combination of cisplatin plus paclitaxel (TP therapy) have a better survival as compared to patients treated with a combination of cisplatin plus cyclophosphamide (CP therapy), but this advantage has not been demonstrated in optimally debulked patients. We performed a retrospective study to compare the effectiveness of TP therapy and CP therapy in optimally debulked patients. STUDY DESIGN: From 1991 to 1996, 87 consecutive patients with advanced ovarian cancer treated in the University Hospital Utrecht and the St. Antonius Hospital were included in the study. Overall survival (OS) of patients treated with TP or CP were compared. Multivariable Cox-regression analysis was used to calculate a hazard rate ratio (HRR) for OS. RESULTS: In the study period, 51 patients were treated with CP, and 36 patients were treated with TP. In the 18 patients with a tumorrest >2cm, there was a clear, but not statistically significant benefit from TP. In 69 patients with a tumorrest <or=2cm, life expectancy was not increased in patients treated with TP as compared to patients treated with CP (HRR 0.9 (95% CI 0.4-1.9)). CONCLUSION: We could not show that ovarian cancer patients with residual disease of <or=2cm who were treated with TP had better survival as compared to patients who were treated with CP. Taking into account the high costs of treatment with TP, a randomized trial comparing the effects of TP therapy and CP therapy in optimally debulked patients is warranted.

Adult↗
PubMed2001

Aromatase and COX-2 expression in human breast cancers.

We have investigated aromatase and the inducible cyclooxygenase COX-2 expression using immunocytochemistry in tumors of a series of patients with advanced breast cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102 breast cancers. This is similar to the percentage previously reported for aromatase activity. Interestingly, aromatase was expressed in a variety of cell types, including tumor, stromal, adipose, and endothelial cells. Since prostaglandin E2 is known to regulate aromatase gene expression and is the product of COX-2, an enzyme frequently overexpressed in tumors, immunocytochemistry was performed on the tissue sections using a polyclonal antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2 expression. These results suggest that PGE2 produced by COX-2 in the tumor may be important in stimulating estrogen synthesis in the tumor and surrounding tissue. No correlation was observed between aromatase or COX-2 expression and the response of the patients to aromatase inhibitor treatment. However, only 13 patients responded. Nine of these patients were aromatase positive. Although similar to responses in other studies, this low response rate to second line treatment suggests that tumors of most patients were no longer sensitive to the effects of estrogen. Recent clinical studies suggest that greater responses occur when aromatase inhibitors are used as first line treatment. In the intratumoral aromatase mouse model, expression of aromatase in tumors is highly correlated with increased tumor growth. First line treatment with letrozole was effective in all animals treated and was more effective than tamoxifen in suppressing tumor growth. Letrozole was also effective in tumors failing to respond to tamoxifen, consistent with clinical findings. In addition, the duration of response was significantly longer with the aromatase inhibitor than with tamoxifen, suggesting that aromatase inhibitors may offer better control of tumor growth than this antiestrogen.

Adipocytes↗
PubMed2001

Severe impairment of postprandial cholecystokinin release and gall-bladder emptying and high risk of gallstone formation in acromegalic patients during Sandostatin LAR.

BACKGROUND: Acromegalic patients treated three times daily with subcutaneous injections of the somatostatin analogue octreotide frequently develop gallstones, due to suppressed cholecystokinin release and impaired gall-bladder emptying. AIM: To elucidate the effects of a new long-acting octreotide formulation (Sandostatin LAR) on gall-bladder emptying, cholecystokinin release and gallstone formation. METHODS: Postprandial gall-bladder and gastric emptying were determined by ultrasonography and cholecystokinin release was measured in seven patients on days 0, 14, 28, and 75 (Sandostatin LAR, 20 mg intramuscularly on days 1, 30, and 60). RESULTS: During treatment, fasting gall-bladder volumes increased from 26.5 +/- 3.2 mL to 61.4 +/- 7.5 mL, but postprandial cholecystokinin release and gall-bladder emptying (from 63.9 +/- 3.8% to 12.3 +/- 3.5%) were severely suppressed. Gallstones formed in six out of seven patients within 8 months of treatment. Gastric emptying did not change during the therapy. CONCLUSIONS: The risk of gallstone formation is greatly increased during Sandostatin LAR. This is probably related to profound suppression of cholecystokinin release and gall-bladder emptying.

Acromegaly↗
PubMed2000

[Fabry disease: data from four families].

In 1988 three families were described in this journal with Fabry's disease, an X-linked recessive lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. A fourth family contained four affected men of whom one was unavailable for evaluation. The other three had the same mutation in de alpha-galactosidase gene, notably Gln386Stop, leading to the change of a glutamine codon into a stop codon. Genetic investigation in one of the other families revealed the Met72Arg mutation. The classical symptoms of the disease (angiokeratomata, acroparaesthesias, hypohidrosis and lucid areas in the cornea) are frequently only recognized after a doctor's delay that may be as long as decades. The recognition of this disease is even more important now, as therapeutic possibilities are in sight.

Adult↗
PubMed1999

A patient with diabetes insipidus and periorbital swellings; Erdheim-Chester disease.

Erdheim-Chester disease is a rare multisystem disease in which a progressive xanthogranulomatous infiltration of several tissues can be seen. We describe a woman, known to have diabetes insipidus for ten years, with periorbital, retroperitoneal, mediastinal, axillar and inguinal involvement. On histological examination a granulomatous infiltration of fatty tissue and striated muscle was seen, consisting of Touton giant cells, histiocytes with foamy cytoplasm and lymphocytes. Immunohistochemical staining with CD-1a and S-100 was negative and on electron microscopy no Langerhans granules were seen. These findings led to the diagnosis of Erdheim-Chester disease. She had a good response on steroids. Because of some similar clinical features of Langerhans cell histiocytosis and Erdheim-Chester disease, a histiocyte disorder seems the most probable cause.

Axilla↗
PubMed1999

Strongyloides stercoralis infection: how to diagnose best?

Four patients are described with a Strongyloides stercoralis infection. Several techniques to diagnose this infection are discussed. The so-called Baermann method is emphasised. Especially in chronic infections the combination of serology and the Baermann method seems the best diagnostic approach. Treatment with albendazole or ivermectin are suggested treatments.

Adult↗
PubMed1998

[Taxoids in ovarian and breast carcinoma: the role of the medical profession and the government].

After registration in 1993/1995 of paclitaxel and docetaxel for the treatment of ovarian and mammary carcinomas, the costliness of these drugs caused Dutch hospitals to adopt different policies for their use. This prompted the Minister of Health to ask the professional group of oncological internists to draw up a guideline for the use of taxoids, following which the government decided to supply extra money for the hospitals to use according to this guideline. Meanwhile new, contradictory study results have become known, still unpublished and in part originating from studies not yet conclude. The pharmaceutical industry advocates terminating the current research and maintaining the existing indications. However, patients are entitled to unbiased, complete research findings. The pathway for introducing new expensive drugs should be as follows: the professionals determine the indications for the new drug, the government pays attention to the financial consequences. The pharmaceutical industries should have no voice in the relevant decision-making.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Serum and urine levels of tamoxifen and its metabolites in patients with advanced breast cancer after a loading dose and at steady-state levels.

PURPOSE: To compare serum and urine levels of tamoxifen and metabolites after a loading dose and at the steady state. METHODS: A loading dose of 160 mg of tamoxifen was given to 14 patients with advanced breast cancer. Thereafter a regular daily dose of 30 mg of tamoxifen was given. Serum and urine levels of tamoxifen and metabolites were measured by high-performance liquid chromatography and compared with levels determined in 31 patients with advanced breast cancer at the steady state at a daily dose of 30 mg of tamoxifen. RESULTS: Serum and urine levels (24-h values) of tamoxifen and metabolites were lower (P < 0.05) after a loading dose than at the steady state. The difference was most pronounced for the metabolites, whereas the tamoxifen loading-dose level was near the steady state. CONCLUSION: Tamoxifen steady state can be reached in 1-2 days by the administration of a loading dose of 160 mg of tamoxifen for 2 days. Tamoxifen metabolite steady-state levels are reached regularly after 4 or more weeks during application of a loading dose. Very little tamoxifen or metabolites are excreted into the urine.

Adult↗
PubMed1997

Inhibition of breast cancer tissue aromatase activity and estrogen concentrations by the third-generation aromatase inhibitor vorozole.

In about one-third of advanced breast cancers, estrogen deprivation causes tumor regression. Estrogen concentrations in tumor tissue seem to depend largely on local production. The aromatase enzyme complex is thought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase activity and estrogen concentrations was evaluated. During 7 days preceding mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase activity and estrone and estradiol levels were measured and compared to the values of nine untreated postmenopausal breast cancer patients. In treated patients, median tissue aromatase activity was 89% lower than that in controls (P < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05, respectively). These results support the hypothesis that depleting the tumor of estrogens, thus impairing estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.

Aged↗
PubMed1996

Primary aortoenteric fistula: report of eight new cases and review of the literature.

Primary aortoenteric fistula, a direct communication between the aorta and the intestinal tract, is a rare cause of gastrointestinal hemorrhage. Eight patients who were all treated at one hospital are described, followed by a review of all surgically treated patients reported within the past 10 years. The usual cause is erosion of an atherosclerotic aneurysm into the adherent duodenum, but a wide variety of other causes and localizations have been described. The clinical presentation is usually one of intermittent gastrointestinal hemorrhage resulting in lethal exsanguination within a matter of hours or days. Pain, a pulsatile abdominal mass, or fever may not be present. Endoscopy, arteriography, ultrasound, and CT scan can be useful in the evaluation of these patients, but physical examination and a high index of suspicion remain key to diagnosis. Primary aortoenteric fistula is more often discovered unexpectedly during exploratory laparotomy and is not usually considered as a presumptive preoperative diagnosis. Although contamination is unavoidable, most patients are treated with an in situ vascular graft and primary closure of the intestinal defect with good results.

Aged↗